JBC PeproTech; Our Business is Cytokines!

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on October 24, 2003
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow Supplemental Data
Right arrow All Versions of this Article:
278/43/42170    most recent
M308079200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Yakovleva, L.
Right arrow Articles by Shuman, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yakovleva, L.
Right arrow Articles by Shuman, S.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print August 8, 2003
J. Biol. Chem, 10.1074/jbc.M308079200
Submitted on July 24, 2003
Revised on August 8, 2003
Accepted on August 7, 2003

Site-specific DNA transesterification by vaccinia topoisomerase: Effects of Benzo[a]pyrene-dA, 8-oxoguanine, 8-oxoadenine and 2-aminopurine modifications

Ludmila Yakovleva, Ligeng Tian, Jane M. Sayer, Govind P. Kalena, Heiko Kroth, Donald M. Jerina, and Stewart Shuman

Molecular Biology Program, Sloan-Kettering Institute, New York, NY 10021

Corresponding Author: s-shuman{at}ski.mskcc.org

Vaccinia DNA topoisomerase forms a covalent DNA-(3'-phosphotyrosyl)-enzyme intermediate at a specific target site 5'-C+5C+4C+3T+2T+1pØN-1 in duplex DNA. Here we study the effects of base modifications on the rate and extent of single-turnover DNA transesterification. Chiral trans opened C-10 R and S adducts of benzo[a]pyrene (BP) 7,8-diol 9,10-epoxide were introduced at single N6-deoxyadenosine (dA) positions within the 3’-G+5G+4G+3A+2A+1T-1A-2 sequence of the nonscissile DNA strand. The R and S BPdA adducts intercalate from the major groove on the 5’ and 3’ sides of the modified base, respectively, and perturb local base stacking. We found that R and S BPdA modifications at +1A reduced the transesterification rate by a factor of 700 to 1000 without affecting the yield of the covalent topoisomerase-DNA complex. BPdA modifications at +2A reduced the extent of transesterification and elicited rate decrements of 200-fold and 7000-fold for the S and R diastereomers, respectively. In contrast, BPdA adducts at the -2 position had no effect on the extent of the reaction and relatively little impact on the rate of cleavage. A more subtle probe of major groove contacts entailed substituting each of the purines of the nonscissile strand with its 8-oxo analog. The +3 oxoG modification slowed transesterification 35-fold, whereas other 8-oxo modifications were benign. 8-Oxo substitutions at the -1 position in the scissile strand slowed single-turnover cleavage by a factor of six, but had a even greater slowing effect on religation, which resulted in an increase in the cleavage equilibrium constant. 2-Aminopurine at positions +3, +4 or +5 in the nonscissile strand had no effect on transesterification per se, but had synergistic effects when combined with 8-oxoA at position -1 in the scissile strand. These findings illuminate the functional interface of vaccinia topoisomerase with the DNA major groove.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Biol. Chem.Home page
L. Yakovleva, S. Chen, S. M. Hecht, and S. Shuman
Chemical and Traditional Mutagenesis of Vaccinia DNA Topoisomerase Provides Insights to Cleavage Site Recognition and Transesterification Chemistry
J. Biol. Chem., June 6, 2008; 283(23): 16093 - 16103.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Yakovleva, J. Lai, E. T. Kool, and S. Shuman
Nonpolar Nucleobase Analogs Illuminate Requirements for Site-specific DNA Cleavage by Vaccinia Topoisomerase
J. Biol. Chem., November 24, 2006; 281(47): 35914 - 35921.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. A. Johnson, J. M. Sayer, H. Yagi, S. S. Patil, F. Debart, M. A. Maier, D. R. Corey, J.-J. Vasseur, T. R. Burke Jr., V. E. Marquez, et al.
Effect of DNA Modifications on DNA Processing by HIV-1 Integrase and Inhibitor Binding: ROLE OF DNA BACKBONE FLEXIBILITY AND AN OPEN CATALYTIC SITE
J. Biol. Chem., October 27, 2006; 281(43): 32428 - 32438.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
S. Antony, P. B. Arimondo, J.-S. Sun, and Y. Pommier
Position- and orientation-specific enhancement of topoisomerase I cleavage complexes by triplex DNA structures
Nucleic Acids Res., October 4, 2004; 32(17): 5163 - 5173.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Tian, J. M. Sayer, D. M. Jerina, and S. Shuman
Individual Nucleotide Bases, Not Base Pairs, Are Critical for Triggering Site-specific DNA Cleavage by Vaccinia Topoisomerase
J. Biol. Chem., September 17, 2004; 279(38): 39718 - 39726.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
L. Yakovleva, C. J. Handy, J. M. Sayer, M. Pirrung, D. M. Jerina, and S. Shuman
Benzo[c]phenanthrene Adducts and Nogalamycin Inhibit DNA Transesterification by Vaccinia Topoisomerase
J. Biol. Chem., May 28, 2004; 279(22): 23335 - 23342.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.